- Email: [email protected]
Concurrent small bowel adenocarcinoma and carcinoid tumor in Crohn's disease — Case report and literature review
Journal of Crohn's and Colitis (2011) 5, 461–464
available at www.sciencedirect.com
SHORT REPORT
Concurrent small bowel adenocarcinoma and carcinoid tumor in Crohn's disease — Case report and literature review☆ Doron Boltin a , Zohar Levi a , Marisa Halpern b , Gerald M. Fraser a,⁎ a
Department of Gastroenterology, Rabin Medical Center, Beilinson Campus and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel b Department of Pathology, Rabin Medical Center, Hasharon Campus and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Received 9 February 2011; received in revised form 23 March 2011; accepted 11 April 2011
KEYWORDS Crohn's disease; Adenocarcinoma; Carcinoid; Composite; Collision
Abstract Adenocarcinomas of the large and small bowel, as well as intestinal carcinoid tumors have been reported at increased rates in Crohn's disease. We herein report a rare case of concurrent adenocarcinoma and carcinoid tumor of the small bowel presenting as intestinal obstruction and found incidentally at laparotomy in a 55 year old male with longstanding ileal Crohn's disease. We performed a Medline Pubmed search for cases of synchronous or composite adenocarcinoma and carcinoid tumor in the setting of Crohn's disease and identified four similar cases. Concurrent adenocarcinoma and carcinoid tumor occurred both in newly diagnosed and longstanding Crohn's disease, most commonly involved the terminal ileum and presented with symptoms mimicking Crohn's disease. Diagnosis was made incidentally at laparotomy in all cases. Lymph node involvement was variable. Clinicians should be aware of this rare entity for expeditious surgical intervention. © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
1. Introduction Abbreviations: CD, Crohn's disease; SBA, small bowel adenocarcinoma. ☆ Conflicts of interest: The authors have no conflicts of interest to declare. ⁎ Corresponding author at: 39 Jabotinsky St., Petah Tikva 49100, Israel. Tel.: +972 39377241; fax: +972 39377206. E-mail address: [email protected] (G.M. Fraser).
Patients with Crohn's disease (CD) have an increased risk of developing large and small bowel adenocarcinoma compared to the general population.1–3 CD patients similarly have an increased risk of developing carcinoid tumors of the gastrointestinal tract.4–9 We herein describe a rare case of concurrent small bowel adenocarcinoma and carcinoid tumor in a patient with CD presenting with disease exacerbation.
1873-9946/$ - see front matter © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.crohns.2011.04.006
462
Figure 1 Segment of TI with a thickened wall, narrow lumen and proximal dilatation.
After reviewing the existing medical literature we identify four similar cases and summarize their clinical features. A possible link between the pathogenesis of these neoplasms and CD is explored.
2. Case report A 55 year old Caucasian male presented at the emergency department with right lower quadrant (RLQ) abdominal pain and fever. He had suffered from Crohn's disease from the age of 24, treated with oral mesalamine 2.4 g daily. Three prior admissions due to obstructive symptoms (5, 8 and 11 years earlier) were each managed conservatively. At the current presentation the patient denied altered bowel movements, vomiting, rectal bleeding or weight loss. Abdominal examination revealed mild RLQ tenderness without rigidity, guarding or masses. Initial blood work showed hemoglobin 12.7 g/dL (normocytic) without leucocytosis, electrolyte disturbances or altered liver function tests. Abdominal CT demonstrated a segment of terminal ileum (TI) with a thickened wall, narrow lumen and proximal dilatation (Fig. 1). Adjacent was an inflammatory mass with infiltration of the mesenteric fat and several enlarged lymph nodes. The patient was treated with
Figure 2 Mass adjacent to TI with infiltration of mesenteric fat and enlarged lymph node.
D. Boltin et al.
Figure 3
Villous adenoma in the terminal ileum.
intravenous steroids and antibiotics for a presumptive diagnosis of CD exacerbation. The patient responded to the given treatment and was discharged, however, returned 10 days later with identical symptoms. The patient was again treated conservatively and discharged only to return several days later due to abdominal pain. At this time a colonoscopy was performed which revealed no mucosal abnormalities in the colon. The ileocecal valve was distorted and appeared fibrosed, precluding intubation of the terminal ileum (TI). At operation there was a stricturing lesion in the distal 15 cm of the TI which was excised together with a 13 cm segment including cecum and ascending colon. Small bowel histology revealed findings typical of CD including fissures, ulcerations, granulomas and a panmural inflammatory infiltrate. On the ulcerated small bowel mucosa was a villous adenoma with adjacent signet ring cell carcinoma (Fig. 2) involving all of the 16 lymph nodes examined. Surgical margins were clear. Infiltrating the muscularis propria were medium sized cells with prominent nucleoli and coarse staining for neuroendocrine markers including chromogranin (Fig. 3) and synaptophisin. Immunohistochemisty staining for MLH1, MSH2, MSH6 and PMS2 was positive, excluding mismatch repair (MMR) gene mutation (Fig. 4). The postoperative course was uneventful. PET-Dotatoc scan was negative and the patient was referred to oncology for adjuvant chemotherapy.
Figure 4
Signet ring carcinoma in the terminal ileum.
Concurrent Adenocarcinoma and Carcinoid Tumor Table 1
463
Characteristics of all reported cases of concurrent adenocarcinoma and carcinoid tumor in CD.
Author (Ref)
Year Sex/age CD duration (y)
Diagnosis
Surgical indication
Site
Size
Nodal Metastasis spread
Van Landingham10 Hock11 Auber12 Cioffi13 Case Report
1983 1993 1998 2005 2010
laparotomy laparotomy laparotomy laparotomy laparotomy
bloody stools RLQ pain perforation, fistula obstruction obstruction
TI cecum TI TI TI
5 foci, 5–10 mm 3 cm – – –
+ – + – +
F/71 F/55 M/37 F/64 M/55
presentation 20 y 2 mo 7y 31 y
– – – – –
Abbreviations: ref, reference; RLQ, right lower quadrant; CD, Crohn's disease; TI, terminal ileum; y, years; mo, months.
3. Discussion We conducted an English language literature review by searching the Medline Pubmed database from 1966 to 2010 using the key terms “Crohn's disease”, “adenocarcinoma”, “carcinoid tumor” and “composite” in order to identify case reports of synchronous or composite adenocarcinoma and carcinoid tumor in the setting of CD. We identified 4 additional cases of concurrent adenocarcinoma and carcinoid tumor in CD (Table 1).10–13 Patients with CD have an incidence of colorectal carcinoma 0.9–2.2 times that of the general population.1,2 Although the relative incidence of small bowel adenocarcinoma (SBA) in CD is 3.4–66.7 fold higher than the general population, these tumors are rare, with only 178 cases described in the literature.1,3 SBA occurs more often in young CD patients (mean age 46 years) with longstanding disease (median 15 years), and carries a poor prognosis (mean survival 24 months).14 Independent predictors of SBA in CD include age and intestinal obstruction.15 Prolonged salicylate use and small bowel resection may be protective.16 Carcinoid tumors in the setting of CD are rare. Including our case, there have been 52 reported cases of carcinoid tumor in CD patients, including one case described by Crohn himself.4–9 CD is associated with a 14.9 fold incidence of carcinoid tumor compared to incidental carcinoids found in appendectomy specimens from healthy subjects.4 However, as most carcinoid tumors are found incidentally at laparotomy their true incidence in CD is unknown. This is confounded by the fact that carcinoids may mimic CD with non-specific gastrointestinal symptoms, weight loss and abdominal pain or mass. These entities may be difficult to distinguish radiologically and CD may even cause a falsepositive octreotide scan.17,18 It is unclear whether there is a connection between the pathogeneses of CD and carcinoid tumors. It has been postulated that proinflammatory cytokines in CD cause hyperstimulation and hyperplasia of enteroendocrine cells.19 Recently the role of chromogranin A (CgA) has been questioned.20 CgA is a seromarker of neuroendocrine tumors which may be elevated in IBD patients. Plasma CgA levels rise in parallel to the inflammatory cascade and correlate with TNF-α levels and disease activity. CgA and CgA-related peptides such as vasostatin and catestatin have a net inhibitory effect on the inflammatory process, dampening the effects of TNF-α, probably by improving endothelial cell function.21,22 The concurrence of SBA and carcinoid in the 5 cases described may represent composite or collision tumors, both
rare but well recognized phenomena in tumors throughout the gastrointestinal tract.23,24 Composite neuroendocrine tumors arise from pleuripotent stem cells with bidirectional differentiation. Current WHO classification of small bowel neuroendocrine tumors categorizes these tumors into1: welldifferentiated neuroendocrine tumor2; low-grade malignant carcinoma3; high-grade malignant carcinoma and4 mixed tumor: adenocarcinoma/neuroendocrine carcinoma.25 Alternatively, it is possible that the histological picture in our case represents a collision tumor, that is, juxtaposition of two discrete neoplasms. The term “adenoendocrine tumor” has been used to describe neoplasms that fall in the spectrum between composite and collision tumors, reflecting the reality that composite tumors and collision tumors are difficult to distinguish histologically.26,27 These tumors tend to behave more like adenocarcinomas than carcinoid tumors, and have a generally poor prognosis,28 however in the cases reviewed there is no data regarding longterm survival. Our literature review demonstrates that these tumors present in young patients at various stages of CD, with symptoms that masquerade as CD exacerbation. Ileoscopy and biopsy may be key to enable early diagnosis before nodal spread. However, where ileoscopy is not feasible, expeditious surgical intervention should be considered.
References 1. Jess T, Gamborg M, Matzen P. Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol 2005;100:2724–9. 2. Von Roon A, Reese G, Teare J. The risk of cancer in Patients with Crohn's disease. Dis Colon Rectum 2007;50:839–55. 3. Seirafi M, Cazals-Hatem D, Bouhnik Y. Adenocarcinoma revealing ileal Crohn's disease. Clin Gastroenterol Hepatol 2010, doi: 10.1016/j.cgh.2010.10.029 published online Nov 9. 4. West NE, Wise PE, Herline AJ. Carcinoid tumors are 15 times more common in patients with Crohn's disease. Inflamm Bowel Dis 2007;13:1129–34. 5. Owczarek D, Cibor D, Szczepański W. Concomitant carcinoid tumor and papillary urothelial neoplasm of low malignant potential in a patient with Crohn's disease: a case report. Eur J Gastroenterol Hepatol 2008;20:1231–4. 6. Gidwani AL, Blake G. Four pathologies in one. Ir J Med Sci 2008;177:77–8. 7. Hazzan D, Eckstein JG, Steinhagen R. Carcinoid tumorand Crohn's ileitis. Isr Med Assoc J 2005;7:674. 8. Hwang H, Doyle J, Chai B. Incidental malignant carcinoid within Crohn ileitis. Can J Surg 2009;52:E58–9.
464 9. Crohn BB, Yarnis H. Complications of regional ileitis. Regional ileitis. New York: Grune & Stratton; 1958. p. 112–6. 10. Van Landingham SB, Kluppel S, Symmonds Jr R, Snyder SK. Coexisting carcinoid tumor and Crohn's disease. J Surg Oncol 1983;24:310–4. 11. Hock YL, Scott KW, Grace RH. Mixed adenocarcinoma/carcinoid tumour of large bowel in a patient with Crohn's disease. J Clin Pathol 1993;46:183–5. 12. Auber F, Gambiez L, Desreumaux P, Mudry J, Lecomte-Houcke M, Cortot A, Quandalle P, Colombel JF. Mixed adenocarcinoid tumor and Crohn's disease. J Clin Gastroenterol 1998;26:353–4. 13. Cioffi U, De Simone M, Ferrero S, Ciulla MM, Lemos A, Avesani EC. Synchronous adenocarcinoma and carcinoid tumor of the terminal ileum in a Crohn's disease patient. BMC Cancer 2005;5:157. 14. Palascak-Juif V, Bouvier AM, Cosnes J. Small bowel adenocarcinoma in patients with Crohn's disease compared with small bowel adenocarcinoma denovo. Inflamm Bowel Dis 2005;11: 828–32. 15. Ruffolo C, Scarpa M, Polese L. Clinical presentation and diagnosis of intestinal adenocarcinoma in Crohn's disease: analysis of clinical predictors and of the life-time risk. J Gastrointest Surg 2010;14:1746–51. 16. Piton G, Cosnes J, Monet E. Risk factors associated with small bowel adenocarcinoma in Crohn's disease: a case–control study. Am J Gastroenterol 2008;103:1730–6. 17. Fernandez A, Tabuenca O, Peteiro A. A “false positive” octreoscan in ileal Crohn's disease. World J Gastroenterol 2008;14:5349–52. 18. Marko J, Lamba R, Miller F, Buchman A, Spies S, Nikolaidis P. Octreoscan positive Crohn's disease mimicking an ileal carcinoid tumor. J Clin Gastroenterol 2008;42:66–8. 19. Le Marc'hadour F, Bost F, Peoc'h M, Roux JJ, Pasquier D, Pasquer B. Carcinoid tumour complicating inflammatory bowel disease.
D. Boltin et al.
20.
21.
22.
23.
24.
25.
26.
27.
28.
A study of two cases with review of the literature. Pathol Res Pract 1994;190:1185–92. Sciola V, Massironi S, Conte D, Caprioli F, Ferrero S, Ciafardini C, Peracchi M, Bardella MT, Piodi L. Plasma chromogranin a in patients with inflammatory bowel disease. Inflamm Bowel Dis 2009;15:867–71. Helle KB, Corti A, Metz-Boutigue MH. The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties. Cell Mol Life Sci 2007;64:2863–86. Blois A, Srebro B, Mandalà M. The chromogranin A peptide vasostatin-I inhibits gap formation and signal transduction mediated by inflammatory agents in cultured bovine pulmonary and coronary arterial endothelial cells. Regul Pept 2006;135:78–84. Doğan L, Karaman N, Bozdoğan N, Atalay C, Yilmaz KB. A case report of composite adenoendocrine carcinoma of the cecum: clinical and pathological evaluation. Turk J Gastroenterol 2009;20:153–4. Jain M, Das KK. Concurrent occurrence of terminal ileum carcinoid tumor and cecal adenocarcinoma: a collision tumor or composite tumor? Indian J Pathol Microbiol 2009;52:285–6. Rindi G, Capella C, Solcia E. Introduction to a revised clinicopathological classification of neuroendocrine tumors of the gastroenteropancreatic tract. Q J Nucl Med 2000;44:13–21. Lewin KJ. The endocrine cells of the gastrointestinal tract. The normal endocrine cells and their hyperplasias. Part I. Pathol Annu 1986;21:1–27. Compton C, Fenoglio-Preiser CM, Pettigrew N, Fielding LP. American Joint Committee on Cancer prognostic factors consensus conference: colorectal working group. Cancer 2000;88:1735–57. Levendoglu H, Cox CA, Nadimpalli V. Composite (adenocarcinoid) tumors of the gastrointestinal tract. Dig Dis Sci 1990;35: 519–25.
available at www.sciencedirect.com
SHORT REPORT
Concurrent small bowel adenocarcinoma and carcinoid tumor in Crohn's disease — Case report and literature review☆ Doron Boltin a , Zohar Levi a , Marisa Halpern b , Gerald M. Fraser a,⁎ a
Department of Gastroenterology, Rabin Medical Center, Beilinson Campus and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel b Department of Pathology, Rabin Medical Center, Hasharon Campus and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Received 9 February 2011; received in revised form 23 March 2011; accepted 11 April 2011
KEYWORDS Crohn's disease; Adenocarcinoma; Carcinoid; Composite; Collision
Abstract Adenocarcinomas of the large and small bowel, as well as intestinal carcinoid tumors have been reported at increased rates in Crohn's disease. We herein report a rare case of concurrent adenocarcinoma and carcinoid tumor of the small bowel presenting as intestinal obstruction and found incidentally at laparotomy in a 55 year old male with longstanding ileal Crohn's disease. We performed a Medline Pubmed search for cases of synchronous or composite adenocarcinoma and carcinoid tumor in the setting of Crohn's disease and identified four similar cases. Concurrent adenocarcinoma and carcinoid tumor occurred both in newly diagnosed and longstanding Crohn's disease, most commonly involved the terminal ileum and presented with symptoms mimicking Crohn's disease. Diagnosis was made incidentally at laparotomy in all cases. Lymph node involvement was variable. Clinicians should be aware of this rare entity for expeditious surgical intervention. © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
1. Introduction Abbreviations: CD, Crohn's disease; SBA, small bowel adenocarcinoma. ☆ Conflicts of interest: The authors have no conflicts of interest to declare. ⁎ Corresponding author at: 39 Jabotinsky St., Petah Tikva 49100, Israel. Tel.: +972 39377241; fax: +972 39377206. E-mail address: [email protected] (G.M. Fraser).
Patients with Crohn's disease (CD) have an increased risk of developing large and small bowel adenocarcinoma compared to the general population.1–3 CD patients similarly have an increased risk of developing carcinoid tumors of the gastrointestinal tract.4–9 We herein describe a rare case of concurrent small bowel adenocarcinoma and carcinoid tumor in a patient with CD presenting with disease exacerbation.
1873-9946/$ - see front matter © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.crohns.2011.04.006
462
Figure 1 Segment of TI with a thickened wall, narrow lumen and proximal dilatation.
After reviewing the existing medical literature we identify four similar cases and summarize their clinical features. A possible link between the pathogenesis of these neoplasms and CD is explored.
2. Case report A 55 year old Caucasian male presented at the emergency department with right lower quadrant (RLQ) abdominal pain and fever. He had suffered from Crohn's disease from the age of 24, treated with oral mesalamine 2.4 g daily. Three prior admissions due to obstructive symptoms (5, 8 and 11 years earlier) were each managed conservatively. At the current presentation the patient denied altered bowel movements, vomiting, rectal bleeding or weight loss. Abdominal examination revealed mild RLQ tenderness without rigidity, guarding or masses. Initial blood work showed hemoglobin 12.7 g/dL (normocytic) without leucocytosis, electrolyte disturbances or altered liver function tests. Abdominal CT demonstrated a segment of terminal ileum (TI) with a thickened wall, narrow lumen and proximal dilatation (Fig. 1). Adjacent was an inflammatory mass with infiltration of the mesenteric fat and several enlarged lymph nodes. The patient was treated with
Figure 2 Mass adjacent to TI with infiltration of mesenteric fat and enlarged lymph node.
D. Boltin et al.
Figure 3
Villous adenoma in the terminal ileum.
intravenous steroids and antibiotics for a presumptive diagnosis of CD exacerbation. The patient responded to the given treatment and was discharged, however, returned 10 days later with identical symptoms. The patient was again treated conservatively and discharged only to return several days later due to abdominal pain. At this time a colonoscopy was performed which revealed no mucosal abnormalities in the colon. The ileocecal valve was distorted and appeared fibrosed, precluding intubation of the terminal ileum (TI). At operation there was a stricturing lesion in the distal 15 cm of the TI which was excised together with a 13 cm segment including cecum and ascending colon. Small bowel histology revealed findings typical of CD including fissures, ulcerations, granulomas and a panmural inflammatory infiltrate. On the ulcerated small bowel mucosa was a villous adenoma with adjacent signet ring cell carcinoma (Fig. 2) involving all of the 16 lymph nodes examined. Surgical margins were clear. Infiltrating the muscularis propria were medium sized cells with prominent nucleoli and coarse staining for neuroendocrine markers including chromogranin (Fig. 3) and synaptophisin. Immunohistochemisty staining for MLH1, MSH2, MSH6 and PMS2 was positive, excluding mismatch repair (MMR) gene mutation (Fig. 4). The postoperative course was uneventful. PET-Dotatoc scan was negative and the patient was referred to oncology for adjuvant chemotherapy.
Figure 4
Signet ring carcinoma in the terminal ileum.
Concurrent Adenocarcinoma and Carcinoid Tumor Table 1
463
Characteristics of all reported cases of concurrent adenocarcinoma and carcinoid tumor in CD.
Author (Ref)
Year Sex/age CD duration (y)
Diagnosis
Surgical indication
Site
Size
Nodal Metastasis spread
Van Landingham10 Hock11 Auber12 Cioffi13 Case Report
1983 1993 1998 2005 2010
laparotomy laparotomy laparotomy laparotomy laparotomy
bloody stools RLQ pain perforation, fistula obstruction obstruction
TI cecum TI TI TI
5 foci, 5–10 mm 3 cm – – –
+ – + – +
F/71 F/55 M/37 F/64 M/55
presentation 20 y 2 mo 7y 31 y
– – – – –
Abbreviations: ref, reference; RLQ, right lower quadrant; CD, Crohn's disease; TI, terminal ileum; y, years; mo, months.
3. Discussion We conducted an English language literature review by searching the Medline Pubmed database from 1966 to 2010 using the key terms “Crohn's disease”, “adenocarcinoma”, “carcinoid tumor” and “composite” in order to identify case reports of synchronous or composite adenocarcinoma and carcinoid tumor in the setting of CD. We identified 4 additional cases of concurrent adenocarcinoma and carcinoid tumor in CD (Table 1).10–13 Patients with CD have an incidence of colorectal carcinoma 0.9–2.2 times that of the general population.1,2 Although the relative incidence of small bowel adenocarcinoma (SBA) in CD is 3.4–66.7 fold higher than the general population, these tumors are rare, with only 178 cases described in the literature.1,3 SBA occurs more often in young CD patients (mean age 46 years) with longstanding disease (median 15 years), and carries a poor prognosis (mean survival 24 months).14 Independent predictors of SBA in CD include age and intestinal obstruction.15 Prolonged salicylate use and small bowel resection may be protective.16 Carcinoid tumors in the setting of CD are rare. Including our case, there have been 52 reported cases of carcinoid tumor in CD patients, including one case described by Crohn himself.4–9 CD is associated with a 14.9 fold incidence of carcinoid tumor compared to incidental carcinoids found in appendectomy specimens from healthy subjects.4 However, as most carcinoid tumors are found incidentally at laparotomy their true incidence in CD is unknown. This is confounded by the fact that carcinoids may mimic CD with non-specific gastrointestinal symptoms, weight loss and abdominal pain or mass. These entities may be difficult to distinguish radiologically and CD may even cause a falsepositive octreotide scan.17,18 It is unclear whether there is a connection between the pathogeneses of CD and carcinoid tumors. It has been postulated that proinflammatory cytokines in CD cause hyperstimulation and hyperplasia of enteroendocrine cells.19 Recently the role of chromogranin A (CgA) has been questioned.20 CgA is a seromarker of neuroendocrine tumors which may be elevated in IBD patients. Plasma CgA levels rise in parallel to the inflammatory cascade and correlate with TNF-α levels and disease activity. CgA and CgA-related peptides such as vasostatin and catestatin have a net inhibitory effect on the inflammatory process, dampening the effects of TNF-α, probably by improving endothelial cell function.21,22 The concurrence of SBA and carcinoid in the 5 cases described may represent composite or collision tumors, both
rare but well recognized phenomena in tumors throughout the gastrointestinal tract.23,24 Composite neuroendocrine tumors arise from pleuripotent stem cells with bidirectional differentiation. Current WHO classification of small bowel neuroendocrine tumors categorizes these tumors into1: welldifferentiated neuroendocrine tumor2; low-grade malignant carcinoma3; high-grade malignant carcinoma and4 mixed tumor: adenocarcinoma/neuroendocrine carcinoma.25 Alternatively, it is possible that the histological picture in our case represents a collision tumor, that is, juxtaposition of two discrete neoplasms. The term “adenoendocrine tumor” has been used to describe neoplasms that fall in the spectrum between composite and collision tumors, reflecting the reality that composite tumors and collision tumors are difficult to distinguish histologically.26,27 These tumors tend to behave more like adenocarcinomas than carcinoid tumors, and have a generally poor prognosis,28 however in the cases reviewed there is no data regarding longterm survival. Our literature review demonstrates that these tumors present in young patients at various stages of CD, with symptoms that masquerade as CD exacerbation. Ileoscopy and biopsy may be key to enable early diagnosis before nodal spread. However, where ileoscopy is not feasible, expeditious surgical intervention should be considered.
References 1. Jess T, Gamborg M, Matzen P. Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol 2005;100:2724–9. 2. Von Roon A, Reese G, Teare J. The risk of cancer in Patients with Crohn's disease. Dis Colon Rectum 2007;50:839–55. 3. Seirafi M, Cazals-Hatem D, Bouhnik Y. Adenocarcinoma revealing ileal Crohn's disease. Clin Gastroenterol Hepatol 2010, doi: 10.1016/j.cgh.2010.10.029 published online Nov 9. 4. West NE, Wise PE, Herline AJ. Carcinoid tumors are 15 times more common in patients with Crohn's disease. Inflamm Bowel Dis 2007;13:1129–34. 5. Owczarek D, Cibor D, Szczepański W. Concomitant carcinoid tumor and papillary urothelial neoplasm of low malignant potential in a patient with Crohn's disease: a case report. Eur J Gastroenterol Hepatol 2008;20:1231–4. 6. Gidwani AL, Blake G. Four pathologies in one. Ir J Med Sci 2008;177:77–8. 7. Hazzan D, Eckstein JG, Steinhagen R. Carcinoid tumorand Crohn's ileitis. Isr Med Assoc J 2005;7:674. 8. Hwang H, Doyle J, Chai B. Incidental malignant carcinoid within Crohn ileitis. Can J Surg 2009;52:E58–9.
464 9. Crohn BB, Yarnis H. Complications of regional ileitis. Regional ileitis. New York: Grune & Stratton; 1958. p. 112–6. 10. Van Landingham SB, Kluppel S, Symmonds Jr R, Snyder SK. Coexisting carcinoid tumor and Crohn's disease. J Surg Oncol 1983;24:310–4. 11. Hock YL, Scott KW, Grace RH. Mixed adenocarcinoma/carcinoid tumour of large bowel in a patient with Crohn's disease. J Clin Pathol 1993;46:183–5. 12. Auber F, Gambiez L, Desreumaux P, Mudry J, Lecomte-Houcke M, Cortot A, Quandalle P, Colombel JF. Mixed adenocarcinoid tumor and Crohn's disease. J Clin Gastroenterol 1998;26:353–4. 13. Cioffi U, De Simone M, Ferrero S, Ciulla MM, Lemos A, Avesani EC. Synchronous adenocarcinoma and carcinoid tumor of the terminal ileum in a Crohn's disease patient. BMC Cancer 2005;5:157. 14. Palascak-Juif V, Bouvier AM, Cosnes J. Small bowel adenocarcinoma in patients with Crohn's disease compared with small bowel adenocarcinoma denovo. Inflamm Bowel Dis 2005;11: 828–32. 15. Ruffolo C, Scarpa M, Polese L. Clinical presentation and diagnosis of intestinal adenocarcinoma in Crohn's disease: analysis of clinical predictors and of the life-time risk. J Gastrointest Surg 2010;14:1746–51. 16. Piton G, Cosnes J, Monet E. Risk factors associated with small bowel adenocarcinoma in Crohn's disease: a case–control study. Am J Gastroenterol 2008;103:1730–6. 17. Fernandez A, Tabuenca O, Peteiro A. A “false positive” octreoscan in ileal Crohn's disease. World J Gastroenterol 2008;14:5349–52. 18. Marko J, Lamba R, Miller F, Buchman A, Spies S, Nikolaidis P. Octreoscan positive Crohn's disease mimicking an ileal carcinoid tumor. J Clin Gastroenterol 2008;42:66–8. 19. Le Marc'hadour F, Bost F, Peoc'h M, Roux JJ, Pasquier D, Pasquer B. Carcinoid tumour complicating inflammatory bowel disease.
D. Boltin et al.
20.
21.
22.
23.
24.
25.
26.
27.
28.
A study of two cases with review of the literature. Pathol Res Pract 1994;190:1185–92. Sciola V, Massironi S, Conte D, Caprioli F, Ferrero S, Ciafardini C, Peracchi M, Bardella MT, Piodi L. Plasma chromogranin a in patients with inflammatory bowel disease. Inflamm Bowel Dis 2009;15:867–71. Helle KB, Corti A, Metz-Boutigue MH. The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties. Cell Mol Life Sci 2007;64:2863–86. Blois A, Srebro B, Mandalà M. The chromogranin A peptide vasostatin-I inhibits gap formation and signal transduction mediated by inflammatory agents in cultured bovine pulmonary and coronary arterial endothelial cells. Regul Pept 2006;135:78–84. Doğan L, Karaman N, Bozdoğan N, Atalay C, Yilmaz KB. A case report of composite adenoendocrine carcinoma of the cecum: clinical and pathological evaluation. Turk J Gastroenterol 2009;20:153–4. Jain M, Das KK. Concurrent occurrence of terminal ileum carcinoid tumor and cecal adenocarcinoma: a collision tumor or composite tumor? Indian J Pathol Microbiol 2009;52:285–6. Rindi G, Capella C, Solcia E. Introduction to a revised clinicopathological classification of neuroendocrine tumors of the gastroenteropancreatic tract. Q J Nucl Med 2000;44:13–21. Lewin KJ. The endocrine cells of the gastrointestinal tract. The normal endocrine cells and their hyperplasias. Part I. Pathol Annu 1986;21:1–27. Compton C, Fenoglio-Preiser CM, Pettigrew N, Fielding LP. American Joint Committee on Cancer prognostic factors consensus conference: colorectal working group. Cancer 2000;88:1735–57. Levendoglu H, Cox CA, Nadimpalli V. Composite (adenocarcinoid) tumors of the gastrointestinal tract. Dig Dis Sci 1990;35: 519–25.